This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Study the effects of Nef on protein trafficking and viral infectivity in primary cultures of human cells. Nef is a significant contributor to the virulence of HIV-1. A variety of phenotypes associated with NEF-expression in continuous human cells lines including its ability to down-regulate CD4 and class I MHC from the cell surface and to optimize viral infectivity have been studied. Recent improvements in cell-transfection methods now allow extension of these studies to the most relevant cells, primary human T lymphocytes. T cell activation may influence the properties of Nef. This hypothesis is best tested in non-transformed cells.